A Structural View of αB-crystallin Assembly and Amyloid Aggregation

Abstract

The major len protein αB-crystallin (αB) is an intracellular chaperone. It belongs to the family of small heat shock proteins (sHsps) which plays a critical role in maintaining protein homeostasis and preventing protein aggregation, especially under stress conditions. Dysfunction of αB is closely related to cataract, and many neurodegenerative diseases including Alzheimer's, Parkinson's, and Creutzfeldt-Jakob disease. Due to the extremely heterogeneous and polydispersed nature of αB, it remains unclear how αB self-assemblies and prevents its client proteins from aggregation. In this minireview, we summarize the structural studies of αB in self-assembly, chaperoning client proteins and amyloid aggregation. We also mention the recent progress in identification of small molecules preventing αB aggregation for potential cataract treatment. This review highlights the polymorphic structures of αB under different conditions and its wide-spectrum chaperone activities, and sheds light on understanding the complex relationship among αB, client proteins and the related diseases.

Keywords: amyloid aggregation; atomic structure; cataract; neurodegenerative diseases; small heat shock proteins; αB-crystallin.